In recent years there have been major advances in the treatment of primary tumors through the use of surgery, chemotherapy, and radiation therapy. Nevertheless, therapeutic failures are frequent and usually due to metastatic spread. At the time of diagnosis, more than half of all cancers have already metastasized. Research over the past decade has provided important information about basic events in the pathogenesis of metastasis. However, little is known about the molecular basis of metastasis. In order to study genes involved in metastasis, the technique of gene transfer, also termed transfection, has been employed by us. The use of the gene transfer technique reveals a DNA segment from a human metastatic tumor that is associated with the metastatic phenotype. Introduction of these sequences into tumorigenic non-metastatic mouse cells causes these cells to become highly metastatic. Specific aims of the proposed project will be: 1) to isolate by molecular cloning a DNA segment that confers metastatic capability, thereby demonstrating a molecular correlate of the metastatic phenotype; 2) to investigate the nature of this DNA segment conferring metastatic capability, to determine if this gene is related to a known cellular oncogene or if it represents a novel gene; 3) to isolate the counterpart gene from normal DNA in order to determine the mechanism of activation of this proto-metastatic gene; 4) to identify the cellular product associated with this metastasis-inducing gene and to examine the expression of this product in various cell types and tissues.